Fig. 1.

A schematic depiction of the gut milieu in which the interaction between hosts and microorganisms occurs. Enteric microorganisms have different regional preferences along the length of the intestine with different biochemical environments such as oxygen and pH. Interactions between the intestinal epithelium and microorganisms affect these biochemical environments. For example, microbial fermentation of dietary fibers produces SCFAs, reducing pH, while butyrate utilization in the colonocytes consumes oxygen, lowering oxygen concentrations and thus allowing for the growth of strict anaerobes. Microbial growth, viability, and virulence expressions are affected by the surrounding environment. Moreover, intestinal homeostasis is maintained by the interaction between intestinal microbiota and immune cells. Given that iPSCs-derived organoids retain small intestinal properties, caution is needed when studying commensals with preference to the large intestine in iPSCs-derived organoids. For better modeling interactions between the gut and microorganisms using intestinal organoids, it would be necessary to consider various gut environments (i.e., pH, oxygen, microbial metabolites, glucose, immune cells) as well as the regional preference of the microorganisms. AdSCs: Adult stem cells, iPSCs: inducible pluripotent stem cells.